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Elucidation of alternative developmental pathway of NKT cells from CD4/CD8 double-negative thymocytes

Research Project

Project/Area Number 24790490
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

DASHTSOODOL Nyambayar  国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (50443057)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNKT / 胸腺 / 分化経路 / CD1d / thymus / development / precursor / ナチュラルキラーT(NKT)細胞 / 分化 / 前駆細胞
Outline of Final Research Achievements

Currently it is thought that NKT cells are generated from CD4/CD8 double-positive (DP) thymocytes by selection on CD1d, a process termed the DP pathway. However, it is still unknown whether NKT cells develop exclusively by the DP pathway in a manner closely resembling that of conventional T cells, or some alternatives to this pathway exist. Here we provide genetic evidences demonstrating the presence of an alternative developmental pathway of NKT cells from CD4/CD8 double-negative (DN) stage thymocytes that is before the DP stage by using the DP-specific Rag2 deletion and genetic fate-mapping mouse models. Furthermore, we found that NKT cells generated by the DN pathway possess characteristics of Th1-biased cytotoxic effector cells suggesting this developmental pathway gives rise preferentially to Th1-type NKT cells. Our present findings provide new insights in understanding the development of NKT cells in the thymus, which seems to be different from that of conventional T cells.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014 2013 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire.2016

    • Author(s)
      Dashtsoodol N, Shigeura T, Ozawa R, Harada M, Kojo S, Watanabe T, Koseki H, Nakayama M, Ohara O, Taniguchi M.
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 4 Pages: 1-10

    • DOI

      10.1371/journal.pone.0153347

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Discovery of NKT cells and development of NKT cell-targeted anti-tumor immunotherapy2015

    • Author(s)
      Taniguchi M, Harada M, Dashtsoodol N, Kojo S.
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 91 Issue: 7 Pages: 292-304

    • DOI

      10.2183/pjab.91.292

    • NAID

      130005088948

    • ISSN
      0386-2208, 1349-2896
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature NKT cell.2014

    • Author(s)
      Ren Y, Dashtsoodol N, Watarai H, Koseki H, Quan C, Taniguchi M.
    • Journal Title

      International Immunology

      Volume: 26 Issue: 10 Pages: 551-561

    • DOI

      10.1093/intimm/dxu057

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature natural killer T cell.2014

    • Author(s)
      Ren Y, Dashtsoodol N, Watarai H, Koseki H,Quan C, Taniguchi M.
    • Journal Title

      Int. Immunol.

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] A validation of the requirement for Vα14 NKT cells for tumor rejection using newly generated Traj18-deficient mice with undisturbed T cell receptor repertoire.2015

    • Author(s)
      Dashtsoodol N, Shigeura T, Watanabe T, Harada M, Kojo S, Endo T, Ohara O, Koseki H, Taniguchi M.
    • Organizer
      CD1-MR1 2015
    • Place of Presentation
      Mantra Lorne, Victoria, Australia
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of the cell with Th1-type NKT cell potential in the DN1 thymic fraction.2013

    • Author(s)
      Dashtsoodol N, Harada M, Endo TA, Ren Y, Seino K, Ohara O, Carey J, Germany-Partarrieu M, Taniguchi M.
    • Organizer
      7th INTERNATIONAL SYMPOSIUM ON CD1 AND NKT CELLS
    • Place of Presentation
      Tours, France
    • Related Report
      2013 Research-status Report
  • [Presentation] Transcription factor c-Maf is indispensable for the development of Interleukin-17 producing RORγt-positive invariant NKT cells.2013

    • Author(s)
      Dashtsoodol N, Ren Y, Harada M, Ishige A, Aihara M, Shigeura T, Ozawa R, Yamanaka H, Seino K, Taniguchi M.
    • Organizer
      7th INTERNATIONAL SYMPOSIUM ON CD1 AND NKT CELLS
    • Place of Presentation
      Tours, France
    • Related Report
      2013 Research-status Report
  • [Remarks] 統合生命医科学研究センター 免疫制御戦略研究グループ 研究紹介

    • URL

      http://www.riken.jp/research/labs/ims/immune_reg/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 統合生命医科学研究センター免疫制御戦略研究グループ 研究紹介

    • URL

      http://www.riken.jp/research/labs/ims/immune_reg/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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